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Low Grade Glioma

Low-grade gliomas (LGGs) are a diverse group of WHO grade I - WHO grade II primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course.

Epidemiology

Low grade gliomas (LGGs) are generally located in the temporal lobe.

see Temporal lobe low grade glioma.

Classification

With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesenchymal according to the mRNA expression. Low grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed 1).


With the increased understanding of glioma tumour genetics there is a need to understand the changes and their implications for patient management. There has also been an increasing trend for adopting earlier, more aggressive surgical approaches to low grade glioma treatment 2).

Verma and Mehta et al., discuss the recent genomics of gliomas, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy.

They also analyze implications of these “molecular classifications”. They propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data 3).


High risk low grade glioma

By age

Pediatric low grade glioma….

By localization

Low grade midbrain glioma


Histology

They include a number of subtypes:

fibrillary astrocytoma

protoplasmic astrocytoma

gemistocytic astrocytoma

and mixed tumours, e.g. oligoastrocytoma

The term should not be used for a specific, non-infiltrative WHO I tumour of astrocyte-lineage such as pleomorphic xanthoastrocytoma (PXA), subependymal giant cell astrocytoma (SGCA) and pilocytic astrocytoma, as these have different prognosis, treatment and imaging features.

Molecular profile

The most critical molecular alterations (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma 4)

Clinical presentation

Preoperative seizures could reflect intrinsic glioma properties 5).

Most patients experience epileptic seizures as a presenting symptom 6) 7) 8) 9) and cause medically-intractable seizure.

see Incidental low grade glioma

Diagnosis

Arterial spin labelled imaging, DTI, and Proton magnetic resonance spectroscopic imaging are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas 10).

The Apparent Diffusion Coefficient (ADC) values of low-grade (WHO I-II) glioma were higher than that of high-grade (WHO III-IV), but the cell density of low-grade glioma was apparently lower than that of high-grade glioma. The ADC values and density of tumor cells were negatively correlated with WHO malignant grades, while the density of cells of glioma was positively correlated with WHO malignant grades 11).

Usually, low grade gliomas show no increase in tumor rCBV, whereas high grade gliomas demonstrate high relative cerebral blood volume (rCBV) that in some cases even extends outside the contrast-enhancing portions of the tumor 12).

Preoperative rCBV is one of the important prognostic factors significantly connected with survival 13).

Treatment

Outcome

Case series

A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment.

A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas “failed” GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits.

GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS 14).

1)
Hua W, Mao Y. [Advance of molecular subtyping and precise treatment for gliomas]. Zhonghua Wai Ke Za Zhi. 2017 Jan 1;55(1):63-66. doi: 10.3760/cma.j.issn.0529-5815.2017.01.016. Chinese. PubMed PMID: 28056258.
2)
Larsen J, Wharton SB, Romanowski C, McKevitt FM, Bridgewater C, Zaki H, Hoggard N. Low grade glioma: An Update for Radiologists. Br J Radiol. 2016 Dec 7:20160600. [Epub ahead of print] PubMed PMID: 27925467.
3)
Verma V, Mehta MP. Clinical ramifications of “genomic staging” of low-grade gliomas. J Neurooncol. 2016 Sep;129(2):195-9. doi: 10.1007/s11060-016-2192-z. Review. PubMed PMID: 27401152.
4)
Olar A, Sulman EP. Molecular Markers in Low-Grade Glioma-Toward Tumor Reclassification. Semin Radiat Oncol. 2015 Jul;25(3):155-63. doi: 10.1016/j.semradonc.2015.02.006. Epub 2015 Feb 23. Review. PubMed PMID: 26050585; PubMed Central PMCID: PMC4500036.
5)
Smits A, Duffau H. Seizures and the natural history of World Health Organization grade II gliomas: a review. Neurosurgery. 2011;68:1326–1333.
6)
Liigant A, Haldre S, Oun A, et al. Seizure disorders in patients with brain tumors. Eur Neurol. 2001;45:46–51.
7)
Lynam LM, Lyons MK, Drazkowski JF, et al. Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg. 2007;109:634–638.
8)
Rosati A, Tomassini A, Pollo B, et al. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009;93:395–400.
9)
Rudà R, Trevisan E, Soffietti R. Epilepsy and brain tumors. Curr Opin Oncol. 2010;22:611–620.
10)
Fudaba H, Shimomura T, Abe T, Matsuta H, Momii Y, Sugita K, Ooba H, Kamida T, Hikawa T, Fujiki M. Comparison of Multiple Parameters Obtained on 3T Pulsed Arterial Spin-Labeling, Diffusion Tensor Imaging, and MRS and the Ki-67 Labeling Index in Evaluating Glioma Grading. AJNR Am J Neuroradiol. 2014 Jul 3. [Epub ahead of print] PubMed PMID: 24994829.
11)
Chen SD, Hou PF, Lou L, Jin X, Wang TH, Xu JL. The correlation between MR diffusion-weighted imaging and pathological grades on glioma. Eur Rev Med Pharmacol Sci. 2014 Jul;18(13):1904-9. PubMed PMID: 25010621.
12)
Hu L. S. et al. Correlations between perfusion MR imaging cerebral blood volume, microvessel quantification, and clinical outcome using stereotactic analysis in recurrent high-grade glioma. AJNR Am J Neuroradiol 33, 69–76, 10.3174/ajnr.A2743 (2012).
13)
Majchrzak K, Kaspera W, Bobek-Billewicz B, Hebda A, Stasik-Pres G, Majchrzak H, Ładziński P. The assessment of prognostic factors in surgical treatment of low-grade gliomas: a prospective study. Clin Neurol Neurosurg. 2012 Oct;114(8):1135-44. doi: 10.1016/j.clineuro.2012.02.054. Epub 2012 Mar 17. PubMed PMID: 22425370.
14)
Coburger J, Merkel A, Scherer M, Schwartz F, Gessler F, Roder C, Pala A, König R, Bullinger L, Nagel G, Jungk C, Bisdas S, Nabavi A, Ganslandt O, Seifert V, Tatagiba M, Senft C, Mehdorn M, Unterberg AW, Rössler K, Wirtz CR. Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging. Neurosurgery. 2016 Jun;78(6):775-86. doi: 10.1227/NEU.0000000000001081. PubMed PMID: 26516822.
low_grade_glioma.txt · Last modified: 2017/04/30 00:39 by administrador